Antihypertensive drug-associated adverse events in osteoarthritis: a study of a large real-world sample based on the FAERS database.

Background: Hypertension is a common complication in patients with osteoarthritis (OA). There is increasing interest in the relationship between hypertension and OA. However, hypertension has been reported to negatively affect symptoms and quality of life in patients with OA. Therefore, treating hypertension is crucial for patients with OA. However, there is a lack of real-world studies on the effects of medications for treating hypertension on OA. Methods: Data from the FAERS database from January 2004 to December 2023 were extracted for disproportionality analyses, and proportional reporting ratios (PRRs) were used to assess the association between medications for hypertension and all types of arthritis. Adverse event signals were identified and determined using reporting odds ratios (RORs) Adverse event signals were considered to have occurred if a drug-induced adverse event was recorded more than or equal to 3 and the lower limit of the ROR confidence interval was more than 1. We selected five classes of drugs including, calcium channel blockers (CCBs), angiotensin converting enzyme inhibitors (ACEIs), angiotensin receptor blockers (ARBs), thiazide diuretics and ß-blockers and representative drugs were analysed for osteoarthritis-related adverse reactions, and age and gender subgroups were analysed for drugs of significance. We also analysed the occurrence of AEs in relation to time using the Weibull distribution. Results: In terms of overall data, we found significant OA adverse reaction signals only for ARBs among the five drug classes.ARB AEs for spinal osteoarthritis (ROR 4.64, 95% CI 3.62-5.94), osteoarthritis (ROR 3.24 95% CI 2.82-3.72) and gouty arthritis (ROR 3.27 95% CI 1.22-8.75) were the three adverse reactions with the loudest signals. Next, we found that valsartan had strong osteoarthritis adverse reaction signals among the three ARBs, namely, irbesartan, cloxartan, and valsartan. We also analysed age and gender subgroups and found that osteoarthritis signals were strongest in the 18-65 and 65+ population, while females seem to be more prone to valsartan-related OA AEs. Conclusion: ARBs, especially valsartan, have significant positive signals for OA AEs. Therefore, ARB drugs, especially valsartan, should be used with caution when treating patients with OA combined with hypertension.

Establishment and validation of a nomogram predicting the risk of deep vein thrombosis before total knee arthroplasty.

PURPOSE: This study aimed to analyze the independent risk factors contributing to preoperative DVT in TKA and constructed a predictive nomogram to accurately evaluate its occurrence based on these factors. METHODS: The study encompassed 496 patients who underwent total knee arthroplasty at our hospital between June 2022 and June 2023. The dataset was randomly divided into a training set (n = 348) and a validation set (n = 148) in a 7:3 ratio. The least absolute shrinkage and selection operator (LASSO) and multivariate logistic regression analysis were used to screen the predictors of preoperative DVT occurrence in TKA and construct a nomogram. The performance of the predictive models was evaluated using the concordance index (C-index), calibration curves, and the receiver operating characteristic (ROC) curves. Decision curve analysis was used to analyze the clinical applicability of nomogram. RESULTS: A total of 496 patients who underwent TKA were included in this study, of which 28 patients were examined for lower extremity DVT preoperatively. Platelet crit, Platelet distribution width, Procalcitonin, prothrombin time, and D-dimer were predictors of preoperative occurrence of lower extremity DVT in the nomograms of the TKA patients. In addition, the areas under the curve of the ROC of the training and validation sets were 0.935 (95%CI: 0.880-0.990) and 0.854 (95%CI: 0.697-1.000), and the C-indices of the two sets were 0.919 (95%CI: 0.860-0.978) and 0.900 (95%CI: 0.791-1.009). The nomogram demonstrated precise risk prediction of preoperative DVT occurrence in TKA as confirmed by the calibration curve and decision curve analysis. CONCLUSIONS: This Nomogram demonstrates great differentiation, calibration and clinical validity. By assessing individual risk, clinicians can promptly detect the onset of DVT, facilitating additional life monitoring and necessary medical interventions to prevent the progression of DVT effectively.

Tough physically crosslinked poly(vinyl alcohol)-based hydrogels loaded with collagen type I to promote bone regeneration in vitro and in vivo.

Poly(vinyl alcohol) (PVA) hydrogels exhibit great potential as ideal biomaterials for tissue engineering, owing to their non-toxicity, high water content, and strong biocompatibility. However, limited mechanical strength and low bioactivity have constrained their application in bone tissue engineering. In this study, we have developed a tough PVA-based hydrogel using a facile physical crosslinking method, comprising of PVA, tannic acid (TA), and hydroxyapatite (HA). Systematic experiments were conducted to examine the physicochemical properties of PVA/HA/TA hydrogels, including their compositions, microstructures, and mechanical and rheological properties. The results demonstrated that the PVA/HA/TA hydrogels possessed the porous microstructures and excellent mechanical properties. Furthermore, collagen type I (ColI) was used to further improve the biocompatibility and bioactivity of PVA/HA/TA hydrogels. In vitro experiments revealed that PVA/HA/TA/COL hydrogel could offer a suitable microenvironment for the growth of MC3T3-E1 cells and promote their osteogenic differentiation. Meanwhile, the PVA/HA/TA/COL hydrogel demonstrated the ability to promote bone regeneration and osteointegration in a rat femoral defect model. This study provides a potential strategy for the use of PVA-based hydrogels in bone tissue engineering.

Fabrication and characterization of porous, degradable, biocompatible poly(vinyl alcohol)/tannic acid/gelatin/hyaluronic acid hydrogels with good mechanical properties for cartilage tissue engineering.

At present, articular cartilage repair and regeneration remain still one of the most concerned problems due to its poor self-healing capacity. Among the tissue engineering materials, hydrogel is considered an ideal candidate due to its similarity to extracellular matrices. Despite the good biocompatibility of gelatin and hyaluronic acid hydrogels, they are still limited to serve as tissue engineering materials by fast degradation rate and poor mechanical performances. In order to solve these problems, novel polyvinyl alcohol/tannic acid/gelatin/hyaluronic acid (PTGH) hydrogels are prepared by a facile physical crosslinked method. The PTGH hydrogels exhibit a high moisture content (85%) and porosity (87%). Meanwhile, the porous microstructures and mechanical properties (compressive strength: 0.85-2.59 MPa; compressive modulus: 57.88-124.27 kPa) can be controlled by adjusting the mass ratio of PT/GH. In vitro degradation analysis shows that the PTGH hydrogels can be degraded gradually in PBS solution with the presence of lysozyme. For this gel system, based on the hydrogen bonds among molecules, it improved the mechanical properties of gelatin and hyaluronic acid hydrogels. With the degradation of PTGH hydrogels, the release of gelatin and hyaluronic acid can have a continuous effort for the cartilage tissue regeneration and repair. In addition, in vitro cell culture results show that the PTGH hydrogels have no negative effects on chondrocytes growth and proliferation. In all, the PTGH hydrogels exhibit potential applications for articular cartilage tissue repair and regeneration.

A Porous Hydrogel with High Mechanical Strength and Biocompatibility for Bone Tissue Engineering.

Polyvinyl alcohol (PVA) hydrogels are considered to be ideal materials for tissue engineering due to their high water content, low frictional behavior, and good biocompatibility. However, their limited mechanical properties restrict them from being applied when repairing load-bearing tissue. Inspired by the composition of mussels, we fabricated polyvinyl alcohol/hydroxyapatite/tannic acid (PVA/HA/TA) hydrogels through a facile freeze-thawing method. The resulting composite hydrogels exhibited high moisture content, porous structures, and good mechanical properties. The compressive strength and tensile strength of PVA hydrogels were improved from 0.77 ± 0.11 MPa and 0.08 ± 0.01 MPa to approximately 3.69 ± 0.41 MPa and 0.43 ± 0.01 MPa, respectively, for the PVA/HA/1.5TA hydrogel. The toughness and the compressive elastic modulus of PVA/HA/1.5TA hydrogel also attained 0.86 ± 0.02 MJm-3 and 0.11 ± 0.02 MPa, which was approximately 11 times and 5 times higher than the PVA hydrogel, respectively. The PVA/HA/1.5TA hydrogel also exhibited fatigue resistance abilities. The mechanical properties of the composite hydrogels were improved through the introduction of TA. Furthermore, in vitro PVA/HA/1.5TA hydrogel showed excellent cytocompatibility by promoting cell proliferation in vitro. Scanning electron microscopy analysis indicated that PVA/HA/1.5TA hydrogels provided favorable circumstances for cell adhesion. The aforementioned results also indicate that the composite hydrogels had potential applications in bone tissue engineering, and this study provides a facile method to improve the mechanical properties of PVA hydrogel.

miR-29a and the PTEN-GSK3ß axis are involved in aluminum-induced damage to primary hippocampal neuronal networks.

We previously reported that aluminum (Al) can cause a range of neurotoxic injuries including progressive irreversible synaptic structural damage and synaptic dysfunction, and eventually neuronal deaths. Mechanism of Al-induced electrophysiological and neuronal connectivity changes in neurons may indicate damage to the neuronal network. Here, mouse primary hippocampal neurons were cultured on micro-electrode array (MEA)- and high-content analysis (HCA)-related plates, showing that Al exposure significantly inhibited hippocampal neuronal electrical spike activity and neurite outgrowth characterized by a reduction in neurite branching and a decrease in the average total neurite length in relation to both Al dose and time of incubation. In recent years, miR-29a/ phosphatase and tensin homolog (PTEN) have been found to play pivotal roles in the morphogenesis of neurons, it has been confirmed in vitro and in vivo that the PTEN-Glycogen synthase kinase-3ß (GSK-3ß) axis regulates neurite outgrowth. The present study demonstrated that increases in Al exposure and dose gradually reduce miR-29a expression. Up-regulation of miR-29a in the hippocampal neurons by lentivirus transfection reversed the decrease in electrical spike activity and the reduction in both neurite branching and length induced by Al. Moreover, miR-29a suppressed the expression of PTEN and increased the level of phosphorylated Protein Kinase B (p-AKT) and p-GSK-3ß which were inhibited by the Al treatment. This suggests that miR-29a is critically involved in the functional and structural neuronal damage induced by Al and is a potential target for Al neurotoxicity. Moreover, the reduction of neurite length and branching induced by Al exposure was regulated by miR-29a and its target neuronal PTEN-GSK3ß signaling pathway, which also represents a possible mechanism of Al-induced the inhibition of the electrical activity. Collectively, Al-induced damage to the neuronal network occurred through miR-29a-mediated alterations of the PTEN-GSK3ß signaling pathway.